**2. Landmark to development of neonicotinoids and their mode of action**


*Insect Resistance to Neonicotinoids - Current Status, Mechanism and Management Strategies DOI: http://dx.doi.org/10.5772/intechopen.101129*


#### **2.1 Neonicotinoid groups Vs Older groups**

Neonicotinoids have been the most commonly used insecticides since the early 1990s as an alternative to older organophosphate and carbamate insecticides. Neonicotinoids are insecticides that exhibit physicochemical properties, rendering them more useful over other classes of insecticides [10]. Over the last few years, neonicotinoids have been combined with pyrethroids in formulated products, and with diatomaceous earth (e.g., Alpine dust insecticide, with dinotefuran) for the control of insect pests. Moderate to high levels of tolerance/resistance to various neonicotinoids showed by insect pests. Romero and Anderson reported that resistance to neonicotinoids may likely be conferred by the increased enzymatic activities found in these populations. Those findings showed that tolerance or even resistance to neonicotinoids is now present in field and storage pest populations [1, 11].

Neonicotinoids show high acute toxicity to honeybees. The neonicotinoid family includes imidacloprid, clothianidin, and thiamethoxam (the latter is metabolized to clothianidin in the plant and the insect). Recently, imidacloprid has been replaced by thiamethoxam and clothianidin in some parts of the world. To date, neonicotinoids have proved the development of resistance, such as *Myzus persicae* and *Phorodon humuli*. The effects of imidacloprid on *Nilaparvata lugens*, tebufenozide on *Plutella xylostella* and *Spodoptera exigua,* thiamethoxam on *Bemisia tabaci,* trichlorphon on *Bactrocera dorsalis*, imidacloprid on *Spodoptera litura*, and emamectin benzoate on *Chrysoperla carnea* have been reported [12].

The first report of neonicotinoid resistance was published in 1996, describing the low efficacy of imidacloprid against Spanish greenhouse populations of cotton whitefly. Later-generation, show stronger resistance (up to 17-fold in the first 15 generations, but >80-fold resistance after 24 generations, which has been confirmed in some populations of the whitefly (*Bemisia tabaci*) and the Colorado potato beetle (*Leptinotarsa decemlineata*) [13]. Although neonicotinoids are applied as foliar insecticides with possible direct exposure risks to honeybees, a large part of neonicotinoid use consists of seed coating or root drench application [14, 15].

#### **2.2 Mode of action of neonicotinoid**

All neonicotinoids act on the insect central nervous system as agonists of the postsynaptic nicotinic acetylcholine receptors (nAChRs). Neonicotinoids act as agonists on the postsynaptic insect nicotinic acetylcholine receptors (nAChRs), biodegradable substituents which have a much higher affinity on insects than mammals [16, 17]. Neonicotinoid insecticides are highly toxic to many invertebrates, including honey bees, bumblebees, and solitary bees. The neonicotinoids (including imidacloprid, dinotefuran, clothianidin, and thiamethoxam) are nitro functional group (∙NO2) instead of a cyano functional group (∙C∙N) in their molecular structure. This slight difference in their molecular structure affects the toxicity level of neonicotinoids, which bind to an insect receptor site. The nitro-group neonicotinoids are much more toxic to bees than the cyano-group neonics, which include acetamiprid and thiacloprid [11, 13, 18].

*Insecticides - Impact and Benefits of Its Use for Humanity*
